A disease or condition is not a pandemic merely because it is widespread or kills many people; it must also be infectious. For instance, cancer is responsible for many deaths but is not considered a pandemic, because the disease is not infectious or contagious (although certain cases of some types of cancer might be).

WHO pandemic influenza phases

The World Health Organization Global Influenza Preparedness Plan defines the stages of pandemic influenza, outlines the role of the WHO and makes recommendations for national measures before and during a pandemic. The phases are:

Interpandemic period:

Phase 1: No new influenza virus subtypes have been detected in humans.

Phase 2: No new influenza virus subtypes have been detected in humans, but an animal variant threatens human disease.

Pandemic alert period:

Phase 3: Human infection(s) with a new subtype, but no human-to-human spread.

Pandemics and notable epidemics through history

There have been a number of significant pandemics recorded in human history, generally zoonoses which came about with domestication of animals — such as influenza and tuberculosis. There have been a number of particularly significant epidemics that deserve mention above the "mere" destruction of cities:

Peloponnesian War, 430 BC. Typhoid fever killed a quarter of the Athenian troops, and a quarter of the population over four years. This disease fatally weakened the dominance of Athens, but the sheer virulence of the disease prevented its wider spread; i.e. it killed off its hosts at a rate faster than they could spread it. The exact cause of the plague was unknown for many years. In January 2006, researchers from the University of Athens analyzed teeth recovered from a mass grave underneath the city, and confirmed the presence of bacteria responsible for typhoid.

Antonine Plague, 165 – 180. Possibly smallpox brought to the Italian peninsula by soldiers returning from the Near East; it killed a quarter of those infected, and up to five million in all. At the height of a second outbreak (251–266), 5,000 people a day were said to be dying in Rome.

Plague of Justinian, from 541 to 750, was the first recorded outbreak of the bubonic plague. It started in Egypt, and reached Constantinople the following spring, killing (according to the Byzantine chronicler Procopius) 10,000 a day at its height, and perhaps 40% of the city's inhabitants. The plague went on to eliminate a quarter to a half of the human population that it struck throughout the known world. It caused Europe's population to drop by around 50% between 550 and 700.

Black Death, started 1300s. Eight hundred years after the last outbreak, the bubonic plague returned to Europe. Starting in Asia, the disease reached Mediterranean and western Europe in 1348 (possibly from Italian merchants fleeing fighting in the Crimea), and killed 20 to 30 million Europeans in six years; a third of the total population, and up to a half in the worst-affected urban areas.

The First Pandemic 1816 – 1826. Previously restricted to the Indian subcontinent, the pandemic began in Bengal, then spread across India by 1820. It extended as far as China and the Caspian Sea before receding.

The "first" pandemic of 1510 travelled from Africa and spread across Europe.

The "Asiatic Flu", 1889–1890. Was first reported in May of 1889 in Bukhara, Uzbekistan. By October, it had reached Tomsk and the Caucasus. It rapidly spread west and hit North America in December 1889, South America in February–April 1890, India in February-March 1890, and Australia in March–April 1890. It was purportedly caused by the H2N8 type of flu virus, and had a very high attack and mortality rate.

The "Spanish flu", 1918–1919. First identified early in March 1918 in US troops training at Camp Funston, Kansas. By October 1918, it had spread to become a world-wide pandemic on all continents, and eventually infected 2.5 to 5% of the human population, with 20% or more of the world population suffering from the disease to some extent. Unusually deadly and virulent, it ended nearly as quickly as it began, vanishing completely within 18 months. In six months, 25 million were dead; some estimates put the total of those killed worldwide at over twice that number. An estimated 17 million died in India, 500,000 in the United States and 200,000 in the UK. The virus was recently reconstructed by scientists at the CDC studying remains preserved by the Alaskan permafrost. They identified it as a type of H1N1 virus.

The "Asian Flu", 1957–58. An H2N2 caused about 70,000 deaths in the United States. First identified in China in late February 1957, the Asian flu spread to the United States by June 1957.

The "Hong Kong Flu", 1968–69. An H3N2 caused about 34,000 deaths in the United States. This virus was first detected in Hong Kong in early 1968, and spread to the United States later that year. Influenza A (H3N2) viruses still circulate today.

Typhus, sometimes called "camp fever" because of its pattern of flaring up in times of strife. (It is also known as "gaol fever" and "ship fever", for its habits of spreading wildly in cramped quarters, such as jails and ships.) Emerging during the Crusades, it had its first impact in Europe in 1489, in Spain. During fighting between the Christian Spaniards and the Muslims in Granada, the Spanish lost 3,000 to war casualties, and 20,000 to typhus. In 1528, the French lost 18,000 troops in Italy, and lost supremacy in Italy to the Spanish. In 1542, 30,000 people died of typhus while fighting the Ottomans in the Balkans. The disease also played a major role in the destruction of Napoleon's Grande Armée in Russia in 1812. Typhus also killed numerous prisoners in the Nazi concentration camps and Soviet prisoner of war camps during World War II.

Effects of Colonization. Encounters between European explorers and populations in the rest of the world often introduced local epidemics of extraordinary virulence. Disease killed the entire native (Guanches) population of the Canary Islands in the 16th century. Half the native population of Hispaniola in 1518 was killed by smallpox. Smallpox also ravaged Mexico in the 1520s, killing 150,000 in Tenochtitlán alone, including the emperor, and Peru in the 1530s, aiding the European conquerors. Measles killed a further two million Mexican natives in the 1600s. Some believe that the death of 90 to 95 percent of the Native American population of the New World was caused by Old World diseases. As late as 1848–49, as many as 40,000 out of 150,000 Hawaiians are estimated to have died of measles, whooping cough and influenza.

There are also a number of unknown diseases that were extremely serious but have now vanished, so the etiology of these diseases cannot be established. The cause of English Sweat in 16th-century England, which struck people down in an instant and was more greatly feared than even the bubonic plague, is still unknown.

Concern about possible future pandemics

Ebola virus and other quickly lethal diseases

Lassa fever, Rift Valley fever, Marburg virus, Ebola virus and Bolivian hemorrhagic fever are highly contagious and deadly diseases, with the theoretical potential to become pandemics. Their ability to spread efficiently enough to cause a pandemic is limited, however, as transmission of these viruses requires close contact with the infected vector. Furthermore, the short time between a vector becoming infectious and the onset of symptoms allows medical professionals to quickly quarantine vectors, and prevent them from carrying the pathogen elsewhere. Genetic mutations could occur, which could elevate their potential for causing widespread harm; thus close observation by contagious disease specialists is merited.

Antibiotic resistance

Antibiotic-resistant microorganisms, sometimes referred to as "superbugs", may contribute to the re-emergence of diseases which are currently well-controlled. For example, cases of tuberculosis that are resistant to traditionally effective treatments remain a cause of great concern to health professionals. The World Health Organization (WHO) reports that approximately 50 million people worldwide are infected with multiple-drug resistant tuberculosis (MDR TB), with 79 percent of those cases resistant to three or more antibiotics. In 2005, 124 cases of MDR TB were reported in the United States. Extensively drug-resistant tuberculosis (XDR TB) was identified in Africa in 2006, and subsequently discovered to exist in 17 countries, including the United States.

In the past 20 years, common bacteria including Staphylococcus aureus, Serratia marcescens and Enterococcus, have developed resistance to various antibiotics such as vancomycin, as well as whole classes of antibiotics, such as the aminoglycosides and cephalosporins. Antibiotic-resistant organisms have become an important cause of healthcare-associated (nosocomial) infections (HAI). In addition, infections caused by community-acquired strains of methicillin-resistant Staphylococcus aureus (MRSA) in otherwise healthy individuals, have become more frequent in recent years.

HIV infection

HIV — the virus that causes AIDS — is of pandemic proportions, with infection rates as high as 25% in southern and eastern Africa. Effective education about safer sexual practices and bloodborne infection precautions training have helped to slow down infection rates in several African countries sponsoring national education programs. Infection rates are rising again in Asia and the Americas. See AIDS pandemic.

SARS

In 2003, there were concerns that SARS, a new, highly contagious form of atypical pneumonia caused by a coronavirus dubbed SARS-CoV, might become pandemic. Rapid action by national and international health authorities such as the World Health Organization helped slow transmission, and eventually broke the chain of transmission, ending the localized epidemics before they could become a pandemic. The disease has not been eradicated, however, and could re-emerge unexpectedly, warranting monitoring and case reporting of suspicious cases of atypical pneumonia.

Influenza

Wild aquatic birds are the natural hosts for a range of influenza A viruses. Occasionally, viruses are transmitted from these species to other species, and may then cause outbreaks in domestic poultry or (rarely) give rise to a human pandemic.

H5N1

In February 2004, avian influenza virus was detected in birds in Vietnam, increasing fears of the emergence of new variant strains. It is feared that if the avian influenza virus combines with a human influenza virus (in a bird or a human), the new subtype created could be both highly contagious and highly lethal in humans. Such a subtype could cause a global influenza pandemic, similar to the Spanish Flu, or the lower mortality pandemics such as the Asian Flu and the Hong Kong Flu.

From October 2004 to February 2005, some 3,700 test kits of the 1957 Asian Flu virus were accidentally spread around the world from a lab in the US

In May 2005, scientists urgently call nations to prepare for a global influenza pandemic that could strike as much as 20% of the world's population.

In October 2005, cases of the avian flu (the deadly strain H5N1) were identified in Turkey. EU Health Commissioner Markos Kyprianou said: "We have received now confirmation that the virus found in Turkey is an avian flu H5N1 virus. There is a direct relationship with viruses found in Russia, Mongolia and China." Cases of bird flu were also identified shortly thereafter in Romania, and then Greece. Possible cases of the virus have also been found in Croatia, Bulgaria and the United Kingdom.

By November 2007, numerous confirmed cases of the H5N1 strain had been identified across Europe. However, by the end of October only 59 people had died as a result of H5N1 which was atypical of previous influenza pandemics.

Despite sensationalizing media reporting, avian flu cannot yet be categorized as a "pandemic", because the virus cannot yet cause sustained and efficient human-to-human transmission. Cases so far are recognized to have been transmitted from bird to human, but as of December 2006 there have been very few (if any) cases of proven human-to-human transmission. Regular influenza viruses establish infection by attaching to receptors in the throat and lungs, but the avian influenza virus can only attach to receptors located deep in the lungs of humans, requiring close, prolonged contact with infected patients, and thus limiting person-to-person transmission. The current WHO phase of pandemic alert is level 3, described as "no or very limited human-to-human transmission", according to the WHO website.